The overall goal of the research program is to develop protein expression systems, instrumentation, and experimental methods so that NMR spectroscopy can be used to study all of the proteins encoded in a genome. Substantial progress has been made through the development of high-resolution solid-state NMR methods, and it is now possible obtain completely resolved and assigned spectra of proteins in membrane bilayers and virus particles.

Membrane proteins are of particular interest, since they constitute about 30% of a genome, representing a major area of research in structural biology, and present challenging systems for NMR spectroscopy. The HIV-1 accessory protein Vpu is one of the principal systems currently being investigated. Vpu has two biological functions that affect the virulence of AIDS. In its phosphorylated form, Vpu enhances both the processing of the envelope glycoprotein gp160, and the degradation of CD4 molecules in infected cells. The protein also acts as an ion channel, an activity associated with its trans-membrane helix and related to its ability to enhance the budding of new virus particles. Several other membrane proteins are under investigation, including the membrane proteins MerF and MerT responsible for transporting mercury across membranes into the cytoplasm where it is reduced to non-toxic and volatile metallic mercury.

The principal system under investigation is G-protein coupled receptors. With seven trans-membrane helices and about 350-residues they represent a significant technical challenge and motivated us to develop a new method of structure determination, rotationally aligned solid-state NMR. This enables the structures of GPCRs and other membrane proteins to be determined under near-native conditions in liquid crystalline phospholipid bilayers. We have determined the structure of the chemokine receptor CXCR1 using this approach.

Primary Research Area
Biochemistry

Interdisciplinary interests

Biophysics
Macromolecular Structure

Outreach Activities

We utilize the Biotechnology Resource Center as a magnet for training students with diverse

backgrounds, and accelerating their acceptance into mainstream scientific research. An example of visitors in various categories are listed above. These include local high school students, undergraduate students supported by the STARS program, graduate students and postdoctoral scholars.